Enantioseparation of Zolmitriptan by HPLC

Aim To establish a HPLC method for the separation of the enantiomers of zolmitriptan. Methods The separations were performed on Chiralcel OJ column with hexane-ethanol-diethylamine（85：15：0.2） as mobile phase at a flow rate of 0.8 mL·min^-1 and detecttion wavelength of 227 nm at 35 ℃. Several related parameters for separation were studied. Results Baseline separation （Rs 〉 1.5） was easily obtained in the case, and the R-isomer impurity in zolmitriptan was determined. Conclusion The method developed in this study has been successfully applied for quality-control purposes.

Enantioseparation of Several PharmaceuticalRacemates with High PerformanceCapillary electrophoresis

With high performance capillary electrophoresis using -cyclodextrin or its deriveatives as the chiral selectors, five pairs of drug enantiomers were separated, The PH of the back- gmund electrolyte and the chiral selector concentrations were optimized; and the effect of organic modifier on separation of chlorpheniramine enantiomers was also inver

Enantioseparation of Aminoglutethimide by High-speed Countercurrent Chromatography Using Carboxymethly-β-cyclodextrin as Chiral Selector

Enantioseparation of aminoglutethimide was performed by high-speed counter-current chromatography with a two-phase system composed of ethyl acetate： methanol： water = 10： 1： 9. The lower phase contained 20 mmol/L of carboxymethly-β-cyclodextrin as chiral selector. The enantiomers were separated in 1.2 h and identified by chiral HPLC. This method was very efficient for the chiral preparative separation.

Enantioseparation of Dencichine and D-Isomer on L-Cysteine Derivative Phase by Ligand-exchange Chromatography

The enantioseparation of dencichine and its D-isomer was achieved on a novel chiral stationary phase via coating N-（2-hydroxyl-3-octoxyl） propyl-S-benzyl-（L）-cysteine on YWG-C18 phase by ligand exchange chromatography.

Influence of Mobile Phase Composition on the Enantioseparation of Methoxyl Flavanones with Self-prepared CDMPC Column and Chiral Recognition Mechanism

The influence of different alcohol modifiers in mobile phase on the chiral separation of 4-methoxyl flavanone, 5-methoxyl flavanone and 6-methoxyl flavanone on cellulose tris (3, 5-dimethylphenylcarbamate) (CDMPC) column was studied and the chiral recognition mechanism was discussed. Using hexane-tert-butanol (1.31 mol L-1) as the mobile phase, those three methoxyl flavanones were excellently separated on CDMPC chiral column.

Enantioseparation of Three Non-Steroidal Anti-Inflammatory Agents on Chiral Stationary Phase by HPLC

This paper reported the enantioseparation of Naproxen, Ketoprofen and Etodolac on tartardiamide-DMB chiral stationary phase (CHI-DMB) and (R,R) –DNB-DPEDA chiral stationary phase,using hexane as the mobile phase with various modifiers. The influence of the mobile phase composition including the type and concentration of the modifiers in hexane and the structures of the analytes on the chiral separation was studied. The results indicated that the steric structure of the solute, especially the environment of the chiral carbon, was the predominant factor for the chiral recognition. The type, the steric structure and the concentration of the modifiers also influence the retention factor and the resolution. The chiral recognition mechanism of the analytes on CHI-DMB and (R,R) –DNB-DPEDA was also discussed. The hydrogen-bonding interaction played an important role on enantioseparation on CHI-DMB, so did the π-π interaction. On (R,R) –DNB-DPEDA the π-π interaction was the key for the solutes retention and enantioseparation, while hydrogen-bonding interaction was not important. Additionally, it has been demonstrated that enantioselectivity and retention was also dependent upon the nature and functional groups on the aromatic ring of solutes and CSP.

Enantioseparation of 3-chlorophenylglycine enantiomers using Mandyphos-Pd as chiral extractant

Chiral extractant plays a key role in chiral extraction,and considerable efforts have been undertaken for the development of new and efficient chiral extractants in recent years.This work demonstrated for the first time that chiral ferrocenyl diphosphine ligand(Mandyphos-Pd)had considerable ability to enantioseparate 3-Chlorophenylglycine enantiomers with separation factor(α)of 2.64.Mandyphos-Pd concentration and pH had significant influences on enantioselectivity,while operating temperature showed less influence.The extraction experiments can be performed at room temperature(20℃)which had the advantage of energy saving.After optimization,the highest performance factor(pf,0.08376)was obtained at the condition of pH 7.8 and Mandyphos-Pd concentration 1.2 mmol·L^(-1).According to the experimental results,the possible recognition mechanism was discussed.

Simultaneous enantioseparation and simulation studies of atenolol,metoprolol and propranolol on Chiralpak^■IG column using supercritical fluid chromatography

Enantioseparation of threeβ-blockers,i.e.,atenolol,metoprolol and propranolol,was studied on amylose tris(3-chloro-5-methylphenylcarbamate)immobilized chiral stationary phase using supercritical fluid chromatography(SFC).The effect of organic modifiers(methanol,isopropanol and their mixture),column temperature and back pressure on chiral separation ofβ-blockers was evaluated.Optimum chromatographic separation with respect to resolution,retention,and analysis time was achieved using a mixture of CO_(2) and 0.1%isopropyl amine in isopropanol:methanol(50:50,V/V),in 75:25(V/V)ratio.Under the optimized conditions,the resolution factors(Rs)and separation factors(a)were greater than3.0 and 1.5,respectively.Further,with increase in temperature(25-45℃)and pressure(100-150 bars)there was corresponding decrease in retention factors(k),a and Rs.However,a reverse trend(a and Rs)was observed for atenolol with increase in temperature.The thermodynamic data from van’t Hoff plots revealed that the enantioseparation was enthalpy driven for metoprolol and propranolol while entropy driven for atenolol.To understand the mechanism of chiral recognition and the elution behavior of the enantiomers,molecular docking studies were performed.The binding energies obtained from simulation studies were in good agreement with the elution order found experimentally and also with the free energy values.The method was validated in the concentration range of 0.5-10μg/m L for all the enantiomers.The limit of detection and limit of quantitation ranged from 0.126 to 0.137μg/m L and 0.376-0.414μg/m L,respectively.The method was used successfully to analyze these drugs in pharmaceutical preparations.

A chiral metal-organic framework{(HQA)(ZnCl_(2))(2.5H_(2)O)}n for the enantioseparation of chiral amino acids and drugs

Chiral metal-organic frameworks(CMOFs)with enantiomeric subunits have been employed in chiral chemistry.In this study,a CMOF formed from 6-methoxyl-(8S,9R)-cinchonan-9-ol-3-carboxylic acid(HQA)and ZnCl_(2),{(HQA)(ZnCl_(2))(2.5H_(2)O)}n,was constructed as a chiral stationary phase(CSP)via an in situ fabrication approach and used for chiral amino acid and drug analyses for the first time.The{(HQA)(ZnCl_(2))(2.5H_(2)O)}n nanocrystal and the corresponding chiral stationary phase were systematically characterised using a series of analytical techniques including scanning electron microscopy,X-ray diffraction,Fourier transform infrared spectroscopy,circular dichroism,X-ray photoelectron spectroscopy,thermogravimetric analysis,and Brunauer-Emmett-Teller surface area measurements.In opentubular capillary electrochromatography(CEC),the novel chiral column exhibited strong and broad enantioselectivity toward a variety of chiral analytes,including 19 racemic dansyl amino acids and several model chiral drugs(both acidic and basic).The chiral CEC conditions were optimised,and the enantioseparation mechanisms are discussed.This study not only introduces a new high-efficiency member of the MOF-type CSP family but also demonstrates the potential of improving the enantioselectivities of traditional chiral recognition reagents by fully using the inherent characteristics of porous organic frameworks.

Enantioseparation of some Racemic Compounds on Cellulose Tris (3,5-dimethylphenylcarbamate) Chiral Stationary Phase

Seven chiral compounds were resolved on cellulose tris (3,5-dimethylphenylcarbamate) chiral stationary phase (CDMPC-CSP) using n-hexane/alcohol as mobile phase. Solvent strength and structural characteristics of the compounds effecting on the retention and resolution were discussed. Satisfactory separation was obtained.

Enantioseparation of Racemic Naproxen Esters on Cellulose Tris (4-methylbenzoate) Chiral Stationary Phase

Several kinds of racemic naproxen ester were successfully separated on CTMB chiral stationary phase with hexane-ethanol (98:2, vol./vol.) as the mobile phase. The influence of mobile phase composition and structure of racemic naproxen ester on chiral separation was studied and the chiral recognition mechanism of CTMB was discussed.

Hollow fiber liquid-supported membrane technology for enantioseparation of racemic salbutamol by combinatorial chiral selectors

Enantioseparation of salbutamol solute was carried out in liquid-supported membrane by using a polyvinylidene fluoride hollow-fiber module. The enantioselective transport of solute was facilitated by combinatorial chiral selectors, which were dissolved in toluene organic solvent. The effects of molar concentration ratios of salbutamol to combinatorial chiral selectors, and the pH value of buffer solution on enantioseparation were investigated. The results show that when the molar concentration ratio is 2∶1∶1, the maximum separation factor and enantiomer excess are 1.49 and 19.74%, respectively, and the R-enantiomer flux is more than S-enantiomer; the pH value of buffer solution influences the performances of enantioseparartion obviously, and the appropriate range of pH value is 7.07.2.

Bio-inspired enantioseparation for chiral compounds

Biomacromolecules including protein and nucleic acids are considered as promising chiral selectors in the fields of enantioselective separation, owing to their inherent chirality, polymorphous structures, stable physicochemical properties, good biocompatibility as well as susceptible modification and regulation. In this review, firstly,enantioselective recognition mechanism of proteins and nucleic acids toward different enantiomers is discussed,as well as their potential applications on the chiral separation of racemic compounds. Secondly, preparative enantioseparation adopting biomolecule-modified hybrid materials including porous microspheres, magnetic nanoparticles and affinity membranes, are introduced respectively. Finally, novel chiroptical materials constructed on the basis of chiral induction, transfer, amplification and transcription, are recognized as promising candidates in future applications.

Sensitive Method for Enantioseparation of Rivastigmine with Highly Sulfated Cyclodextrin as Chiral Selector by Capillary Electrophoresis

A sensitive method for enantioseparation of a basic drug rivastigmine and determination of its optical impurity by capillary electrophoresis with highly sulfated β-cyclodextrin （HS-β-CD） as the chiral selector is described. In general, enantioseparation of basic chiral compounds is carried out in acidic condition （pH 2.5） to prevent analytes from adsorption on the capillary wall. However, in the case of rivastigmine, the detection sensitivity was too limited to determine the optical impurity of S-rivastigmine lower than 1% when buffer pH was 2.5. It was found that the detection sensitivity was improved 1.6 times just by raising the buffer pH value from 2.5 to 5.8. The poor column efficiency due to the adsorption of the analytes on the capillary wall was resolved by using dynamical coating of the capillary wall with the linear polyacrylamide solution. The experimental parameters such as the concentration of HS-β-CD, buffer pH and buffer ionic strength were optimized, respectively. The method was validated in terms of repeatability, linearity, limit of detection （LOD） and limit of quantitation （LOQ）. Using the present method, the optical purity of nonracemic rivastigmine with the enantiomeric excess （ee） value of 99.14% was determined.

Enantioseparation by HPLC Using an Inorganic Chiral Mesoporous Silica with Highly-ordered Structure

Highly-ordered inorganic chiral mesoporous silica(HOCMS)has attracted substantial interest in recent decades.High performance liquid chromatography(HPLC)is the most important approach for the separation of enantiomers and herein reported an HPLC chiral stationary phase composed of HOCMS.The column was fabricated by conventional high pressure slurry packing.Eighteen racemates,including alcohols,ketones,amines,aldehydes and organic acids,were resolved on the column.Good chiral separations of hydrobenzoin,metoprolol,propranolol hydrochloride,4-methyl-2-pentanol,omeprazole,2,2′-furoin and ketoprofen were obtained.The relative standard devi-ations for five replicate separations of racemates were 0.1%–0.16%for retention time and 1.73%–2.64%for peak areas.The results suggest that HOCMS is a promising candidate for preparation of chiral stationary phases for HPLC.

In-situ and one-step preparation of protein film in capillary column for open tubular capillary electrochromatography enantioseparation

In this wo rk,the phase-transitioned BSA(PTB)film using the mild and fast fabrication process adhered to the capillary inner wall uniformly,and the fabricated PTB film-coated capillary column was applied to realize open tubular capillary electrochromatography(OT-CEC)enantioseparation.The enantioseparation ability of PTB film-coated capillary was evaluated with eight pairs of chiral analytes including drugs and neurotransmitters,all achieving good resolution and symmetrical peak shape.For three consecutive runs,the relative standard deviations(RSD)of migration time for intra-day,inter-day,and column-tocolumn repeatability were in the range of 0.3%-3.5%,0.2%-4.9%and 2.1%-7.7%,respectively.Moreover,the PTB film-coated capillary column ran continuously over 300 times with high separation efficiency.Therefore,the coating method based on BSA self-assembly supramolecular film can be extended to the preparation of other proteinaceous capillary columns.

Chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin immobilized on porous silica for enantioseparation

In this work, a series of chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin bonded stationary phase for high performance liquid chromatography(HPLC) were synthesized via a simple one-pot synthesis approach. Various racemates(aryl alcohols, flavanones, triazoles, benzoin, etc.) were well separated on the tricarboxylic acid modified chiral stationary phases in both normal and reversed modes with good reproducibility and stability, and the influence of mobile phase composition on resolution(R_(s)) were deeply investigated. The RSD values of Rsfor repeatability and column-to-column were below 1.28% and 3.05%, respectively. Hence, the fabrication of tricarboxylic acid modified chiral stationary phase(CSPs) is a new efficient strategy to improve the application of β-cyclodextrin as CSPs in the field of chromatography.

A quasi-dual-chiral-channel specific enantioseparation material

Researchers engrossed in enantioseparation keep seeking for versatile chiral separation selectors.This work proposes a concept of quasi-dual-chiral-channel(QDCC)enantioseparation platform,where the surface sequentially grafted quinine(QN)and functional cyclodextrin(CD)can imitate two independent chiral channels without mutual interference to achieve wide spectrum chiral resolution.Chiral separation results combined with molecular docking simulation indicates that the different interaction mode of QN and functional CD layer renders QDCC the wide separation capability.This work provides a valuable insight into the rational design of versatile enantioseparation materials.

A New Biselector Chiral Stationary Phase Derived from Tartaric Acid and Its Enantioseparation Evaluation

Two chiral selectors were synthesized from tartaric acid. The selectors were simultaneously immobilized on 3-aminopropyl silica gel to obtain a new biselector chiral stationary phase （CSP） in order to determine the influence of selector structure of biselector CSPs on the chiral recognition capability. For comparison, the single-selector CSP was also prepared. The biselector CSP shows an improved overall chiral recognition capability in comparison with the single-selector CSP. During the enantioseparation, temporary diastereoisomers are likely formed by complexation between a chiral analyte and the two selectors on the biselector CSP. The functional groups in the two selectors are complementary in electronic effect and/or in steric hindrance for the chiral recognition.